Leukotrienes (LTs) are potent pro-inflammatory mediators produced by the metabolism of arachidonic acid. They are believed to have a critical role in mediating the inflammatory response and consequently may be involved in the etiology of several diseases including asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Therefore, the compounds of this invention, which inhibit the biosynthesis of the LTs, have potential use in the treatment of these diseases.
The biosynthesis of leukotrienes and their pathophysiology have been well documented. Many investigators have been seeking to block the pathophysiological effects of the leukotrienes, either by blocking their biosynthesis or by blocking their activity at the receptor level. Two recent reviews (J. H. Musser and A. F. Kreft. J. Med. Chem., 1992, 35, 2501 and A. Shaw and R. D. Krell J. Med. Chem., 1991, 34, 1235) describe the status of research in these areas, including results of clinical trials. Results of clinical trials such as those cited in these articles support the concept that agents which block the biosynthesis or activity of the leukotrienes will be useful in asthma and possibly other inflammatory diseases mentioned above.